title: S100A9 differentially modifies phenotypic states of neutrophils, macrophages, and dendritic cells: implications for atherosclerosis and adipose tissue inflammation.
abstract: BACKGROUND
  S100A9 is constitutively expressed in neutrophils, dendritic cells, and monocytes; is associated with acute and chronic inflammatory conditions; and is implicated in obesity and cardiovascular disease in humans. Most of the constitutively secreted S100A9 is derived from myeloid cells. A recent report demonstrated that mice deficient in S100A9 exhibit reduced atherosclerosis compared with controls and suggested that this effect was due in large part to loss of S100A9 in bone marrow-derived cells.
  
  
  RESULTS
  To directly investigate the role of bone marrow-derived S100A9 in atherosclerosis and insulin resistance in mice, low-density lipoprotein receptor-deficient, S100A9-deficient bone marrow chimeras were generated. Neither atherosclerosis nor insulin resistance was reduced in S100A9-deficient chimeras fed a diet rich in fat and carbohydrates. To investigate the reason for this lack of effect, myeloid cells were isolated from the peritoneal cavity or bone marrow. S100A9-deficient neutrophils exhibited a reduced secretion of cytokines in response to toll-like receptor-4 stimulation. In striking contrast, S100A9-deficient dendritic cells showed an exacerbated release of cytokines after toll-like receptor stimulation. Macrophages rapidly lost S100A9 expression during maturation; hence, S100A9 deficiency did not affect the inflammatory status of macrophages.
  
  
  CONCLUSIONS
  S100A9 differentially modifies phenotypic states of neutrophils, macrophages, and dendritic cells. The effect of S100A9 deficiency on atherosclerosis and other inflammatory diseases is therefore predicted to depend on the relative contribution of these cell types at different stages of disease progression. Furthermore, S100A9 expression in nonmyeloid cells is likely to contribute to atherosclerosis.
authors.affiliation: Department of Pathology, Diabetes and Obesity Center of Excellence, 815 Mercer St, University of Washington, Seattle, WA 98109-8055, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Averill
authors.forename: Shelley
authors.initials: S
authors.lastname: Barnhart
authors.forename: Lev
authors.initials: L
authors.lastname: Becker
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Renee C
authors.initials: RC
authors.lastname: Leboeuf
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hamerman
authors.forename: Clemens
authors.initials: C
authors.lastname: Sorg
authors.forename: Claus
authors.initials: C
authors.lastname: Kerkhoff
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D040501:Calgranulin A / Q000502:physiology; D040502:Calgranulin B / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D010641:Phenotype; D011973:Receptors, LDL / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D008070:Lipopolysaccharides; D011973:Receptors, LDL; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4